ABX464 Maintenance Therapy for Ulcerative Colitis

Recruiting at 591 trial locations

Overseen By Chris Rabbat

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Abivax S.A.

Disqualifiers: Crohn's disease, Colon cancer, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

1050 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests ABX464, an experimental treatment, to determine its effectiveness for people with ulcerative colitis, a condition causing long-lasting inflammation in the digestive tract. The trial evaluates whether taking ABX464 once daily is safe and effective for those who haven't found success with other treatments like steroids or biologics. Individuals who have tried other ulcerative colitis treatments but still experience symptoms might be suitable for this study. Participants will receive either ABX464 or a placebo to compare results over time. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it mentions that certain medications and procedures for ulcerative colitis are prohibited during the study. It's best to discuss your current medications with the study team to see if they are allowed.

Is there any evidence suggesting that ABX464 is likely to be safe for humans?

Research has shown that ABX464, also known as obefazimod, is generally safe. Studies have found that people with ulcerative colitis, a condition causing inflammation and sores in the colon, who took ABX464 for up to five years did not encounter any new safety issues. This indicates the treatment did not cause unexpected side effects. In an earlier study, patients reported that the drug was well-tolerated, meaning they did not experience significant discomfort or negative reactions. These findings suggest that ABX464 is likely safe for long-term use in managing ulcerative colitis. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for ulcerative colitis?

Researchers are excited about ABX464 for ulcerative colitis because it offers a novel approach compared to existing treatments like mesalamine, corticosteroids, and biologics. Unlike these standard therapies, ABX464 works by enhancing the body's natural anti-inflammatory processes through a unique mechanism involving the modulation of RNA splicing, which can potentially reduce inflammation more effectively. Additionally, ABX464's oral administration provides a convenient alternative to injections or infusions, making it easier for patients to adhere to their treatment regimen. This new mechanism and delivery method have generated interest due to their potential to provide better disease management and improved patient quality of life.

What evidence suggests that ABX464 might be an effective treatment for ulcerative colitis?

Research shows that ABX464, also known as obefazimod, may help treat moderate-to-severe ulcerative colitis. Earlier studies found it safe and effective, with many participants experiencing a significant reduction in symptoms after just eight weeks. For example, in recent trials called ABTECT-1 and ABTECT-2, obefazimod achieved its main goal of reducing symptoms. Additionally, more than half of the patients in an earlier study responded positively by the eighth week. This trial will evaluate ABX464 in various dosages, including 25mg and 50mg, for both responder and non-responder subjects at the end of induction, as well as a placebo group. This suggests that ABX464 could be a helpful treatment for those who haven’t had success with other therapies. ^{2 5 6 7 8}

Who Is on the Research Team?

Severine Vermeire, MD, PhD

Principal Investigator

UZ Leuven, Belgium

Bruce Sands, MD, PhD

Principal Investigator

Mount Sinai Health System Digestive Disease Institute, New York USA

Are You a Good Fit for This Trial?

This trial is for people with moderate to severe ulcerative colitis who didn't get better with standard or advanced treatments. They must have finished a previous ABX464 study and can't be planning pregnancy soon. Participants need valid endoscopy results, agree to use effective contraception, sign consent forms, and commit to the study schedule.

Inclusion Criteria

Subjects must have completed the induction treatment study (ABX464-105 or ABX464-106), and patients' clinical response status must be available.

Subjects should be affiliated to a health insurance policy whenever required by a participating country or state.

I have had an endoscopy with results read by a central reader.

Exclusion Criteria

I plan to try for a baby in the next year.

Subjects who plan to participate in other investigational studies during the maintenance study.

Subjects who permanently discontinued the study treatment during the induction study (either ABX464-105 or ABX464-106).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Maintenance Treatment

Participants receive ABX464 25 mg or 50 mg or placebo once daily for 44 weeks

44 weeks

Long Term Extension

Participants can continue their allocated treatment for up to 4 years after the maintenance phase

4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

End of Study (EOS) visit

What Are the Treatments Tested in This Trial?

Interventions

• ABX464

Trial Overview The trial tests long-term effects of two doses of ABX464 (50mg or 25mg) as daily maintenance therapy compared to a placebo. It's randomized: some get the real drug without knowing if it's high or low dose; others get a fake pill. The treatment lasts 44 weeks followed by an evaluation after another 28 days.

How Is the Trial Designed?

Group I: Long Term Extension Experimental Treatment 1 Intervention

At the end of the maintenance phase (week 44), subjects can continue their allocated treatment for up to 4 years. Once the maintenance phase is unblinded, subjects receiving placebo in the maintenance phase will be allocated to obefazimod 25 mg or can terminate the study.

Group II: ABX464 50mg - Non responder subjects at the end of induction Experimental Treatment 1 Intervention

Subjects will be orally dosed during 44 weeks

Group III: ABX464 25mg - Non responder subjects at the end of induction Experimental Treatment 1 Intervention

Subjects will be orally dosed during 44 weeks

Group IV: ABX464 50mg - Responder subjects at the end of induction Placebo Group 1 Intervention

Subjects will be orally dosed during 44 weeks

Group V: ABX464 25mg - Responder subjects at the end of induction Placebo Group 1 Intervention

Subjects will be orally dosed during 44 weeks

Group VI: Placebo - Responder subjects at the end of induction Placebo Group 1 Intervention

Subjects will be orally dosed during 44 weeks

Who Is Running the Clinical Trial?

Abivax S.A.

Lead Sponsor

Trials

22

Recruited

4,400+

Published Research Related to This Trial

Maintenance therapy for ulcerative colitis (UC) is crucial for preventing relapses and improving quality of life, with current treatments also helping to reduce the need for corticosteroids and elective colectomy.

The review highlights that the use of immunosuppressive therapies is decreasing the necessity for colectomy in UC patients, indicating a shift towards more effective long-term management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and emerging maintenance therapies for ulcerative colitis. O'Connor, A., Moss, AC.[2016]

5-ASA is the primary treatment for mild to moderate ulcerative colitis, effectively inducing and maintaining remission by reducing local immune activity.

For severe flares, corticosteroids are preferred, but to avoid long-term use, biologics with varying safety profiles are available, aiming not just for clinical remission but also for endoscopic and histological remission to enhance quality of life and reduce cancer risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Overview and update on treatment in ulcerative colitis]. Rossier, L., Matter, C.[2023]

Salicylates are the first-line treatment for moderate ulcerative colitis (UC), while corticosteroids are used for inducing remission but not for long-term maintenance, highlighting the importance of tailored treatment strategies based on disease severity.

Vedolizumab, a non-anti-TNF alpha biotherapy, is now available for UC treatment, providing an alternative for patients who are resistant to corticosteroids or require maintenance therapy after thiopurines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of diagnosis and treatment in ulcerative colitis]. Klotz, C., Barret, M., Dhooge, M., et al.[2016]

In a study involving 174 patients with ulcerative colitis, MMX mesalazine at a dose of 2.4 g/day showed a good safety profile, with most adverse events being mild or moderate, and only 3.9% experiencing serious adverse events.

Both once-daily and twice-daily dosing of MMX mesalazine resulted in high rates of clinical and endoscopic remission after 12 months, with 64.4% and 68.5% of patients in remission, respectively, indicating that once-daily dosing is effective and convenient for maintenance therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised trial of once- or twice-daily MMX mesalazine for maintenance of remission in ulcerative colitis. Kamm, MA., Lichtenstein, GR., Sandborn, WJ., et al.[2022]

Effective maintenance treatment for ulcerative colitis requires ongoing therapy even when patients feel better, as this helps prevent flares and long-term complications.

Patient adherence to treatment is crucial; strategies like simplified dosing, reduced co-pays, and strong doctor-patient relationships can significantly improve adherence and, consequently, treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New keys to maintenance treatment in ulcerative colitis. Higgins, PD.[2021]

Citations

1. academic.oup.com academic.oup.com/ecco-jcc/article/19/5/jjaf074/8149142

Obefazimod in patients with moderate-to-severely active ... Obefazimod has demonstrated safety and efficacy in patients with moderate-to-severely active ulcerative colitis (UC) in a phase 2b induction ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40417999/

Obefazimod in patients with moderate-to-severely active ... Obefazimod has demonstrated safety and efficacy in patients with moderate-to-severely active ulcerative colitis (UC) in a phase 2b induction trial.

3. ir.abivax.com ir.abivax.com/news-releases/news-release-details/abivax-announces-positive-phase-3-results-both-abtect-8-week

Abivax Announces Positive Phase 3 Results from Both ... Results from the ABTECT-1 and ABTECT-2 trials demonstrated that obefazimod met its FDA primary endpoint of clinical remission at Week 8 in the 50 mg once-daily ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03093259

Study Details | NCT03093259 | ABX464 in Subjects With ... This Phase IIa study is an 8-week, double-blind, placebo-controlled, randomized study aiming at evaluating the safety and the efficacy of ABX464 given once ...

5. journals.lww.com journals.lww.com/ajg/fulltext/2024/12001/s9_efficacy_and_safety_of_obefazimod_in_patients.10.aspx

S9 Efficacy and Safety of Obefazimod in Patients With... Among the 217 patients who participated in the OLM, 57% (124/217) achieved clinical response at week 8 of the induction trial (CR group), and 43% (93/217) did ...

6. abivax.com abivax.com/pipeline/abx464-ibd-uc/

ABX464 for UC - Abivax No new safety signals were detected in UC patients treated up to five years with oral, once-daily, obefazimod. Obefazimod Mechanism of Action in Ulcerative ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04023396

NCT04023396 | Efficacy and Safety Study of ABX464 as ... This study is an open-label study aiming at evaluating the long-term safety and the efficacy profile of ABX464 given once a day (o.d) at 50 mg in subjects ...

8. ir.abivax.com ir.abivax.com/news-releases/news-release-details/abivax-reports-two-year-efficacy-and-safety-data-obefazimod

Abivax reports two-year efficacy and safety data of obefazimod ... Abivax reports two-year efficacy and safety data of obefazimod phase 2b maintenance trial in ulcerative colitis. April 17, 2023. PDF Version.